Polyanions have long been shown to have strong effects on the activity of lymphoid cells. In our studies, we have shown strong synergies between B cell and T cell mitogens with Dextran Sulfate, a commonly used polyanion. We suggest that polyanions, in an as yet unknown manner, lower the threshold for activation of lymphocytes. We wish to extend our observations and explore the phenomena of the synergy found with polyanions. Does Dextran Sulfate alter dose response profiles or accessory cell requirements for the activation of lymphocytes in vitro? We will use exclusively assays which measure the fraction of cells engaged in clonally measured responses. In addition, using a few clonal assays, we will survey several different kinds of polyanions and polycations to determine the range of molecules that exert these synergies and we will determine if polycations antagonize the influence of polyanions. Using flow cytometry, acridine orange and membrane potential sensitive dyes, we will explore the influence of polyanions on lymphocyte activation. We will also determine where polyanions exert their effects, cell surface or cell interior.